A critical event during an inflammatory response is the recruitment of blood leukocytes to the site of injury, immune response, or infection, resulting in transendothelial migration (TEM). Dysregulation of the inflammatory response is a factor in many diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis, atherosclerosis, asthma, and psoriasis. The TEM of leukocytes from the vasculature into the neighboring tissues has been studied extensively. However, there is limited information regarding the endothelium-dependant mechanisms that may contribute to leukocyte egress at endothelial cell (EC) lateral junctions. [unreadable] [unreadable] The focus of this application is to examine leukocyte egress at endothelial cell-cell junctions, concentrating on the mechanisms that allow the rapid formation of inter-endothelial cell, claps by VE-cadherin during leukocyte TEM. Throughout this study we will make use of the a variety of in vitro molecular, biochemical, immunological, and biological techniques, including adenoviral constructs, fluorescence recovery after photobleaching and leukocyte TEM in flow chamber assays. Specifically, we will determine the 1) the lateral mobility of wild type VE-cadherin and a tailless mutant VE-cadherin in vascular endothelium and 2) examine the lateral mobility of these proteins during leukocyte TEM. [unreadable] [unreadable]